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Sofosbuvir and Daclatasvir for Recurrent Hepatitis C After Liver Transplantation: Potent Antiviral Activity But Lack of Clinical Benefit if Treatment is Given Too Late
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"Sofosbuvir and daclatasvir combination is a highly effective antiviral treatment in LT recipients with severe recurrent hepatitis C and has no interactions with immunosuppressants. However, despite improved liver function in survivors, deaths and severe disease complications occur frequently in this very sick population. These data strongly support that this potent combination must be initiated before the onset of cholestasis or decompensation."
Reported by Jules Levin
EASL 2014 April 9-13 London, UK
A.M. Pellicelli1, R. Lionetti2, M. Montalbano2, C. Durand3, P. Ferenci4, G. D'Offizi2, V. Knop5, A. Telese6, I. Lenci6, A. Andreoli7, S. Zeuzem5, M. Angelico6
1Liver Unit, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy, 2Hepatology, Istituto Nazionale Malattie Infettive 'Lazzaro Spallanzani' IRCCS, Rome, Italy, 3Division Infectious Disease-Department of Medicine, Johns Hopkins University, Baltimore, MD, United States, 4Internal Medicine 3-Gastroenterology and Hepatology, Medical University of Vienna, Wien, Austria, 5Internal Medicine, Goethe University Hospital, Frankfurt, Germany, 6Hepatology, Tor Vergata University, 7Liver Unit, Azienda Ospedaliera San Camillo Forlanini, Rome,Italy, Rome, Italy
Program Abstract
Background and aims: A rapidly effective and safe all-oral therapy is highly desirable to prevent graft loss due to HCV recurrence after liver transplantation (LT). To evaluate, within a compassionate use program, the efficacy and safety of a combination of sofosbuvir (400 mg/day) and daclatasvir (60 mg/day) +/-ribavirin in LT recipients with severe recurrent HCV-related disease.
Methods: Twelve LT recipients (11 HCV genotype 1 and one genotype 4), median MELD score 20 (range: 8-40), including 4 with cholestatic features and 8 with decompensated cirrhosis.
Results: Eleven patients received at least 4 weeks and 7 more than 12 weeks of antiviral therapy. Two patients died due to liver failure and gastrointestinal bleeding (GB), at week 2 (initial MELD: 40) and week 12 (MELD 28), respectively, and a third due to sepsis at week 9 (MELD: 39). Additional four patients experienced severe adverse events (SAE) unrelated to drug therapy (2 bacterial spontaneous peritonitis, GB, pneumonia). Serum HCV RNA was undetectable in 9/11(82%) at week 4 and in 7/7 (100%) at week 12. Serum bilirubin and Child-Pugh score improved significantly at week 12 vs baseline (p=0.02). No calcineurin inhibitor dosage adjustments were necessary.
Conclusions: Sofosbuvir and daclatasvir combination is a highly effective antiviral treatment in LT recipients with severe recurrent hepatitis C and has no interactions with immunosuppressants. However, despite improved liver function in survivors, deaths and severe disease complications occur frequently in this very sick population. These data strongly support that this potent combination must be initiated before the onset of cholestasis or decompensation.
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